To determine the safety, biologic, and clinical benefits of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF; Amgen, Thousand Oaks, CA) after myelosuppressive chemotherapy in acute myeloid leukemia (AML), 108 adult patients with de novo AML were randomized to receive either PEG-rHuMGDF (2.5 microg/kg/d or 5 microg/kg/d) for up to 21 doses (group A), a single dose of 2.5 microg/kg PEG-rHuMGDF, 7 daily doses of 2.5 microg/kg PEG-rHuMGDF (group B), or placebo. The greatest biologic activity was seen in group A with a median peak platelet count of 1,084 x 10(9)/L, occurring at a median 9 days after the last dose of study drug, compared with 517 x 10(9)/L and 390 x 10(9)/L in group B and placebo group, respectively. Thrombocytosis (platelets >1,000 x 10(9)/L) was seen at rates of 52%, 8%, and 9% in groups A, B, and placebo, respectively, but were not associated with any adverse event. There was no effect on median time to transfusion independent platelet recovery (> or = 20 x 10(9)/L). The median time to neutrophil recovery (> or = 500/microL) and red blood cell transfusion requirements were similar in all groups, and there was no apparent stimulation of leukemia. PEG-rHuMGDF was biologically active and well tolerated. Further investigation of dose and scheduling is required, specifically earlier dosing before and during chemotherapy.